NATURE IMMUNOLOGY Blockbuster: Subverting the traditional understanding of immunogenic cell death

A few days ago, the editor introduced a new hot spot in the field of cell death - immunogenic cell death (ICD)
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Regarding immunogenic cell death, NATURE IMMUNOLOGY's review article in April this year mentioned a heavy conclusion, subverting our traditional understanding of immunogenic cell death
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The article suggests the importance of immunogenic cell death in the etiology of non-infectious, non-malignant diseases related to self-reaction
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The idea of ​​immunogenic cell death can be directly scanned for consultation.
In fact, as early as 2017, NATURE REVIEWS IMMUNOLOGY reviewed the mechanism of immunogenic cell death and the knowledge related to its pathophysiology
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But the consensus at the time also focused on the ability of infectious and malignant cells to undergo immunogenic cell death
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However, with the rapid development of related research, the current understanding of immunogenic cell death has been subversive
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In addition, with the advent of two anticancer drugs based on the definition of ICD in the past two years, and the development of multiple clinical trials of immunotherapy combined with ICD, future ICD-related research is destined not to be left out
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A quick look at the important content of the article 1.
Potential impact of ICD in non-infectious, non-malignant diseases Other autoimmune syndromes such as vitiligo do not appear to involve an infectious component as part of the etiology of the disease, strongly pointing to endogenous DAMPs and ICD A (possibly limited level) role in melanocyte-specific CTL initiation
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While formal evidence to support this idea is lacking, it is worth noting that true autoimmunity, as well as various other diseases involving some degree of autoreactivity (eg some forms of cardiomyopathy, metabolic syndrome) may not necessarily be Involves loss of peripheral tolerance to purely "self" antigenic determinants
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Conversely, lesions associated with disease pathogenesis (eg, oxidative stress, hyperglycemia) may promote enzymatic or non-enzymatic alterations of endogenous proteins, resulting in bona fide post-translational neoantigens not covered by central tolerance
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Regardless of the exact antigenic determinants of non-malignant, non-infectious diseases associated with autoreactivity, there is increasing evidence that ICDs and endogenous DAMPs are at least somewhat involved in the etiology of these diseases
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2.
Hallmarks of ICD: antigenicity, adjuvant and environmental immunogenicity comes from two factors, antigenicity and adjuvant, moreover, ICD-driven adaptive immune responses can only be performed correctly in the presence of permissive microenvironmental conditions
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3.
The stress response pathway of ICD Only some cellular stressors can induce true ICD, including selected drugs commonly used in clinical practice
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At the mechanistic level, a common (but not universal) feature of ICD-inducing molecules appears to be their ability to repress transcription
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But how transcriptional repression at this stage triggers ICD-related stress pathways remains unclear
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Fourth, the evolutionary hypothesis of ICD In phylogeny and ontogeny, innate immunity precedes its adaptive counterpart
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Therefore, it is reasonable to speculate that the ICD's ability to mount an antigen-specific response to RCD in mammals was developed in a subsequent wave
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V.
Recovery and Strengthening of ICD to Support Cancer Immune Surveillance Due to local or systemic deficiencies, infected or malignant cells receiving ICD may not attract the attention of immune surveillance
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These deficiencies must be detected and eliminated to restore or enhance ICD-driven immunity in a personalized manner
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VI.
CONCLUSIONS AND OUTLOOK The term ICD has become part of the standard oncology vocabulary, facilitating the development of new therapeutic agents, treatment combinations and personalized strategies
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However, the term has not been used by the scientific community engaged in infectious disease research
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Furthermore, although ICD may be associated with a variety of non-infectious, non-malignant diseases, the term has not been widely accepted in the field
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In the future, omics technologies that can utilize spatial and temporal resolution, as well as 3D video microscopy, are needed to address the complexities of ICDs and generate important information that can be used to modulate ICDs to treat a variety of human diseases
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For ideas related to immunogenic cell death, you can directly scan the code for more information on bioinformatics analysis: 18501230653 (same number on WeChat)